Macrothrombocytopenia in a group of related Norfolk terriers
Department of Veterinary Pathology, Hygiene and Health, University of Milan, Milan 20133, Italy.The Veterinary record 09/2010; 167(13):493-4. DOI: 10.1136/vr.c4782
Article: Inherited platelet disorders[Show abstract] [Hide abstract]
ABSTRACT: To present the latest information on inherited platelet disorders in domestic animals. Research articles and reviews spanning 40 years available on PubMed. Information regarding inherited platelet disorders in people is plentiful and often descriptions of human conditions have led to the identification of similar disorders in veterinary species. There are exceptions, however, in which specific inherited platelet disorders were first described in animals with subsequent identification in people. Many inherited platelet disorders have been documented in animals at the functional and molecular level and that information is presented in this review. Much progress has been made in the past 20 years in the characterization of inherited platelet disorders in animals at the functional, biochemical, and molecular level. The study of inherited platelet disorders has greatly enhanced the understanding of platelet physiology and has led in some instances to the development of platelet inhibitory medications. Characterization of inherited disorders at the molecular level greatly facilitates diagnosis and identification of affected and heterozygous animals thus avoiding propagation of the defect by breeders. When used with available functional and biochemical diagnostic tests, it significantly enhances the quality of care and case management.
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ABSTRACT: Determination of the plateletcrit (PCT) is the most effective way to evaluate platelet mass in dogs, such as Cavalier King Charles spaniel (CKCS) dogs, with macrothrombocytopenia. The IDEXX VetAutoread hematology analyzer, which performs quantitative buffy coat (QBC) analysis, has been validated to determine platelet mass in CKCS dogs. The Advia 2120 reports a PCT, but the validity of this value has not been evaluated for dogs with macrothrombocytopenia. The goal of this study was to validate MPV and PCT determined by the Advia 2120 in dogs, including CKCS dogs, comparing values with those obtained from QBC analysis. Advia PCT was compared with QBC results from 43 CKCS dogs and 15 dogs of other breeds in one study. Advia PCT, platelet count, and MPV were evaluated to identify biologic patterns in 31 clinically healthy CKCS dogs and 66 dogs of 3 other breeds and to generate values used for comparisons. Advia PCT agreed well with QBC results in general, but had a negative bias and appeared to underestimate PCT in CKCS dogs with the lowest PCTs. Advia PCT and MPV results followed expected biologic patterns in CKCS dogs and dogs of other breeds with MPVs being highest in dogs with the lowest platelet counts. Advia 2120 PCT and MPV satisfactorily identified changes in platelet mass and size in CKCS dogs, but PCTs were lower than expected, especially in CKCS dogs with the lowest PCTs, when compared with QBC results.
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ABSTRACT: Background An asymptomatic macrothrombocytopenia, phenotypically similar to asymptomatic inherited macrothrombocytopenia in Cavalier King Charles Spaniels, was described in a group of Norfolk Terriers (NT) from Northern Italy, and isolated cases were also reported in Cairn Terriers (CT).Objectives The purpose of this work was to evaluate for the presence of a genetic defect in the β1-tubulin gene in macrothrombocytopenic NT and CT.Methods Samples from 20 healthy dogs (13 NT and 7 CT) were collected at different institutions in Italy (n = 8), United Kingdom (n = 3), and United States (n = 9). Genomic DNA was harvested from EDTA-anticoagulated blood and all coding areas and exon–intron splice sites in the gene encoding β1-tubulin were amplified and sequenced.ResultsTwelve dogs (9 NT and 3 CT) showed a single nucleotide polymorphism (SNP) in exon 1 at nucleotide position 5 (G5A) that would result in the change of an arginine to a histidine at amino acid position 2 (R2H). Four dogs (3 NT and one Cairn Terrier) were heterozygous for the SNP, and 4 dogs (one Norfolk Terrier and 3 CT) matched the normal canine genome. Homozygous dogs for the SNP were macrothrombocytopenic with platelet counts ranging from 19,000 to 110,000/μL. Heterozygous and normal dogs had normal platelet counts and morphology. None had the CKCS point mutation.Conclusions The β1-tubulin N-terminal amino acids form the nucleotide-binding domain and thus this mutation could affect GTP binding enough to influence platelet formation in homozygous but not in heterozygous dogs. The presence of macrothrombocytopenia only in homozygous affected dogs reveals an association between the SNP and the phenotype.
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